Chapter 40. Approach to Poisoning

Patients with poison exposure and toxicity may present with a spectrum of various clinical signs, symptoms, and problems. Most of these are very straightforward and easily anticipated, but others may be unpredictable or associated with exposure to unidentified substances that hinder the clinician from knowing what to expect. There are, however, general principles that may be employed as a framework on which approach to most poisonings may be based. These are employed when managing adverse effects from poisoning by known or unidentified substances. Less than 5% of poisonings require use of specific antidotes; thorough general supportive care is the most important approach in caring for most poisoned patients.1

The initial principles of management of poisoned patients generally follow the protocol used for the management of urgent and emergent problems. There are some slight differences if the “airway, breathing, circulation” approach is used, with some specific amendments relevant to poison exposures and toxicity. “Airway, breathing, circulation, disability, dextrose, exposure, ECG” comprise the general “A, B, C, D, D, E, E” mantra of poison management. This may differ from other emergency department (ED) management in that “disability” and “exposure,” necessary for patients with trauma, are not essential in most poisoned patients, but can reveal some valuable diagnostic information.

Critical to proper management of poisoning is recognition that poison exposure occurred. When evaluating a poisoned patient, a good approach is to identify the reason of exposure (i.e., intentional, unintentional, misadventure), the type of substance involved (i.e., prescription, over-the-counter, herbal, illicit drug), the formulation (i.e., immediate vs. sustained release), the dose of the substance, the amount of substance involved, the route of exposure (i.e., ingestion, inhalation, intravenous, dermal), the time of exposure (hours since exposure, acute vs. chronic), any potential coingestion, and the severity of exposure.

Obtaining a medical history from the poisoned patient may be difficult, and, therefore, other people such as family members, friends, prehospital personnel, the patient's physician or therapist, or previous medical records may provide crucial information to aid in management. Thorough medical knowledge of all ailments, medical history, medication history, and other medications or substances the patient had access to often provides useful information.

After initial assessment, stabilization, and physical exam, further management may include (1) decontamination, (2) prevention of absorption, (3) administration of antidote, and (4) enhanced elimination of the toxic substance.

Examination of patients with poison exposure and toxicity is often more focused than a general physical examination, with particular attention to areas that are expected to yield useful information (Table 40-1).

Assessment of vital signs, neurologic status, pupils, skin, bowel, and bladder permits the recognition of a toxidrome. A toxidrome, or toxicologic syndrome, is a constellation of signs and symptoms that herald toxicity from a category of poisons. Recognition of the presence of a toxidrome is useful in managing patients with exposure to unidentified substances and is also useful after known exposure to a category of substances known to cause a specific toxidrome.

Traditionally there are four described toxidromes: adrenergic/sympathomimetic, anticholinergic, cholinergic, and opioid. There is also a well-recognized pattern of clinical findings associated with sedative–hypnotic substances. The classes of substances causing toxidromes include:

• Adrenergic (sympathomimetic): sympathomimetic agents capable of α- and/or β-adrenergic agonism, for example, cocaine, amphetamines, theophylline, caffeine, pseudoephedrine, ephedrine, epinephrine, norepinephrine, and methylenedioxymethamphetamine (MDMA) (ecstasy).
• Anticholinergic: substances that block cholinergic receptors, for example, atropine, scopolamine, antihistamines, phenothiazines, cyclic antidepressants, and cyclobenzaprine.
• Cholinergic: substances that afflict cholinergic receptors, for example, organophosphate pesticides and nerve agents, physostigmine, rivastigmine, and nicotine.
• Opioid: substances that afflict opioid receptors, for example, heroin, morphine, hydromorphone, methadone, diphenoxylate, clonidine, and tramadol.
• Sedative–hypnotic: substances that increase GABA activity, for example, benzodiazepines, barbiturates, alcohols, GHB, and zolpidem.

It is important to note that patients presenting with potential toxicity may have mixed clinical picture and may not entirely fall under a specific toxidrome. This is particularly true for patients presenting with polydrug overdoses, or in cases in which an ingested drug has been adulterated with another toxidrome-causing substance (Table 40-2).

The investigations and assays most useful in management of poisoned patients are commonplace in emergency medicine and critical care. Although it is possible to assay for hundreds of substances capable of causing toxicity, the most frequently indicated investigations are familiar to the ED and critical care physicians and are readily available in any setting where emergency and critical care are delivered.

Electrocardiogram

Electrocardiograms are indicated in patients with exposure to substances capable of inducing dysrhythmia, exposure to unidentified substances, and exposures with intent of self-harm. Most often, ECGs obtained in the ED setting for nonpoisoned patients are for the purpose of detecting ischemic changes. For patients with poison exposures and toxicity, evaluation for changes in cardiac conduction, conduction intervals, and dysrhythmia is of greatest interest. Ischemia is certainly of interest if present, but this is not the primary focus of ECG evaluation in patients with poison exposure and toxicity.

The triad of pseudo right bundle branch block consisting of R wave in AVR, S wave in lead I, and S wave in AVL, are highly sensitive indicators of sodium channel blockade resulting from tricyclic antidepressant exposure.2 If these findings are present, prolongation of QRS duration to 100 and 150 milliseconds is predictive of seizure and ventricular dysrhythmia, respectively.3,4

Dysrhythmias may result from toxins too numerous to list. Characteristic changes with ventricular bradydysrhythmia are seen with digoxin and other cardiac glycoside toxicity. Nonspecific ST changes throughout all leads and, occasionally bradycardia accompany lithium toxicity.

Poison-induced dysrhythmias may require very different management from the same dysrhythmia that occurs due to other means. In such cases, use of the “standard” management will be ineffective, and occasionally use of the standard management algorithm will increase morbidity and mortality. Some of these managements are described by the American Heart Association.5 Patients with poison-induced cardiac dysrhythmias should be managed by clinicians familiar with and preferably experienced with these clinical scenarios. (See also the chapter “The Critically Ill Poisoned Patient.”)

Laboratory—Routinely Indicated Assays

Serum glucose measurement and serum electrolyte analysis are the two most indicated lab assays in the management of poisoned patients. These tests allow detection of hypoglycemia, which may result from a variety of poisons, including both agents known to cause hypoglycemia and substances that may cause hyperglycemia and a subsequent hypoglycemic response. Any patient with altered mental status, including depressed or altered sensorium, coma, or agitation, should have immediate bedside assessment of the blood glucose level. This assay provides a result that is immediately interpretable, meaningful to the treating clinicians, and allows an anticipated, appropriate response with administration of dextrose or glucagon. Serum chemistry assessment allows detection of anion gap metabolic acidosis, alterations of sodium, potassium, and serum bicarbonate, and alterations of the other measured substances.

The anion gap is calculated by the following formula: [Na+] − [Cl− + HCO3−], and the normal value is generally accepted to be between 6 and 14 mEq/L.6 Discovery of an anion gap in the poisoned patient should prompt investigation of the cause if unknown. Such causes may be exogenous or endogenous etiologies as represented by the MUDPILES mnemonic: methanol, uremia, diabetic ketoacidosis, paraldehyde/phenformin, iron/inhalants (carbon monoxide, cyanide, and hydrogen sulfide), isoniazid/ibuprofen, lactic acidosis, ethylene glycol/ethanol ketoacidosis, and salicylates/solvents (benzene, toluene)/sympathomimetics/starvation ketoacidosis. Measurement of the serum osmolar gap is occasionally useful in the patient with suspected toxic alcohol ingestion, but has many limitations. The measured serum osmolarity is compared with the calculated serum osmolarity to derive the gap that represents other osmotically active substances. The formula is: Osmcalc = 2[Na+] + (BUN/2.8) + (glucose/18) + (ethanol/4.6). Methanol, ethylene glycol, and numerous other drugs, chemicals, and disease states may contribute to this gap. There is a wide, poorly defined range of “normal” osmolar gap, usually ranging from −5 to +15 mOsm/kg.7,8 Given that the patients' baseline osmolar gap is rarely known, it is difficult to reliably determine if an unmeasured osmotically active substance is present. Thus, the change in this gap as the toxic alcohol is metabolized, in conjunction with the anion gap and any laboratory levels of alcohols, is more important; a “normal” osmolar gap does not rule out exposure to a toxic alcohol.

Additional laboratory assays that are commonly useful include serum acetaminophen level, salicylate level, ethanol level, and blood gas analysis. Serum acetaminophen assays are indicated for any patient with potentially toxic exposure to acetaminophen and any patient with exposure with intent of self-harm, regardless of whether acetaminophen exposure is reported,9 and may be useful in patients with elevation of hepatic transaminases after exposure to unidentified substances.

Serum salicylate levels may aid in detection of undisclosed salicylate exposure. Salicylate toxicity may be identified by clinical findings,10 but these may be obscured by polydrug exposure, other medical ailments, or lack of clinician exposure to salicylate-poisoned patients.11 We advocate routine use of serum salicylate screening in patients with unidentified exposures or exposures with intent of self-harm.

Serum ethanol levels may provide insight into causality of depressed mental status. Although wide variability in patient tolerance to ethanol makes interpretation of serum ethanol level and correlation with degree of depression of consciousness less than fully accurate,12 this assay is a staple of ED assessment of patients with depressed consciousness.

Readers are advised to interpret serum ethanol level with caution. Overlooking other emergent causes of depressed or altered mental status, such as intracranial hemorrhage, encephalitis, or sepsis, by inappropriately attributing the mental state to ethanol exposure is a very common error in emergency medicine. This error routinely results in morbidity and mortality, and is a common cause for legal cases brought against treating physicians. The presence of a serum ethanol level capable of causing intoxication should not cause the clinician to discontinue investigating potential emergent causes of altered or depressed mental status.

Blood gas analysis is useful for a variety of reasons, including to elucidate the type and degree of acidosis or alkalosis, detect dyshemoglobinemias through carboxyhemoglobin or methemoglobin level, and determine oxygen extraction and utilization in poisonings that may result in blockade of oxidative phosphorylation, such as by cyanide. In nearly all cases, with the most common exception of cardiac arrest, venous blood gas sampling has been shown to be nearly equivalent to arterial sampling. The simplest correction or correlation of pH between venous and arterial blood gas samples is performed by adding 0.03 to the venous pH to obtain the arterial pH.13,14 In most cases venous blood gas sampling is adequate,13,14 and arterial blood sampling should only be performed when necessary. An exception to this general rule is evaluation for cyanide or other disruptors of oxidative phosphorylation, in which comparison of simultaneously obtained arterial and venous blood gas samples is used to assess oxygen extraction across the capillary and tissue bed.

Serum creatine phosphokinase may be obtained when a patient exhibits signs of altered temperature regulation and muscle tone such as in the serotonin and neuroleptic malignant syndromes or the sympathomimetic toxidrome. Additionally, many common drugs have the potential to cause rhabdomyolysis, the most well known of which are statins, steroids, theophylline, and doxylamine. Any condition that has the potential to cause trauma or prolonged immobilization, such as the abuse of rapid-onset sedatives, may damage muscle, thereby releasing potentially dangerous amounts of potassium and creatine phosphokinase.

Laboratory—Quantitative Assays

Generally, on exposure to a substance for which a serum concentration, or “level,” may be obtained, such information may potentially be highly useful for management and/or prognosis. Occasionally these are critical to select a specific management, especially hemodialysis, other method of enhanced elimination, or antidote administration.

Laboratory—Drug of Abuse Screening

Laboratory screening for drugs of abuse, commonly amphetamines, cannabinoids (marijuana), cocaine, PCP, and opioids, is the toxicology lab screening that is least useful, most overutilized, and most misunderstood and misinterpreted toxicologic lab assay.15–17 Other than for forensic purposes, lab assay for drugs of abuse is not routinely indicated for patients with exposure to drugs or abuse or for patients with unidentified exposures. As these screenings are only qualitative, they confirm only that exposure to the substance in question that occurred within the previous days or week, depending on the substance. Many such assays are not complete for the respective drug category. A screening assay specific for amphetamine might not detect methamphetamine or MDMA (ecstasy), which are much more widely abused than amphetamine. A typical opioid screening will detect natural opioids but not synthetic opioids, such as methadone, fentanyl, propoxyphene, tramadol, etc. Many commonly abused drugs, such as ketamine and GHB, are not detected by any routine laboratory screening. Many medications known to cause false-positive drug of abuse screening exist. Screening for cocaine is the most accurate of the commonly used drug of abuse screening tests, but the tested metabolite benzoylecgonine typically is detectible in urine for 2–3 days after a single exposure.18

Failure to understand the limitations of drug of abuse screening leads uninformed clinicians to obtain this test, and often to misinterpret the results.

Malicious exposures, exposures in children incapable of volitionally using drugs, and other circumstances for which forensic evidence of drug abuse exposure would be useful should be obtained in consultation with physicians with forensic experience and law enforcement officials.

Imaging

Occasionally, imaging may be useful in evaluation. Some radiodense materials, such as lead, heavy metals, enteric-coated tablets, and ingested packages containing drugs such as cocaine or heroin, may be identified by plain radiography. In some circumstances, abdominal x-ray may reveal radiopaque materials, such as hydrocarbons, that may cause a characteristic “double bubble” sign in the stomach. Two heavy metals particularly amenable to detection by plain films are nonchewable iron tablets and ingested lead containing foreign bodies. The sensitivity of plain x-ray to identify ingested drug packages is very high, and classic findings may include visualization of staples used to hold packs closed, “rosettelike finding” of air trapped in knots where packets are tied, and the “double condom” sign in which air is seen trapped between layers of latex (Figures 40-1 and 40-2).19

Computerized tomography (CT) may also be indicated to identify ingested substances such as ingested drug packages or radiodense materials. In the case of rupture of ingested packages, CT scanning should be performed after surgery to document complete gastrointestinal tract clearance.19

Imaging is useful to evaluate for the consequences of poisoning; examples are chest radiograph that may identify pneumonitis associated with hydrocarbon or other aspiration, abdominal radiograph showing bowel obstruction or perforation, or CT that may provide information about the extent and severity of injury from caustic ingestion.

Endoscopy may provide direct imaging of the airway or GI tract and may be particularly useful in patients with caustic exposures to aid in diagnosis, discharge, and prognosis. We recommend endoscopy with all intentional caustic ingestions and most nonalkali exposures. In children, stridor, or the combination of drooling and vomiting, should prompt endoscopy.20 When indicated, endoscopy should be performed within 8–12 hours and no later than 24 hours.

Decontamination to prevent adverse effects of poison exposure has long been advocated as a poison management strategy. The concept that removing a poison from the body may avert illness is easily understood by laypersons and clinicians alike, and this strategy seems to make common sense. Despite this, repeated and rigorous testing of gastrointestinal decontamination methods has routinely failed to demonstrate any convincing benefit. Gastrointestinal decontamination plays an increasingly small and marginal role in the management of poisoned patients. External decontamination of the skin and eyes continues to play a vital role in some poison management.

External and Ocular Decontamination

When a toxin is on a patient's body, external decontamination should be performed to protect staff from becoming ill and to limit ongoing toxicity to the patient. This is best performed at a designated shower or mass casualty decontamination area near the entrance of the ED. The patient should be completely disrobed; jewelry, watch, etc., should be removed and the entire body or exposed area thoroughly washed. For ocular exposures, the eyes are irrigated with copious isotonic solution (such as normal saline or lactated Ringer's) for at least 30 minutes or until a normal ocular pH is obtained. For full efficacy, a Morgan lens should be used in the affected eye, and ocular anesthetic such as tetracaine or proparacaine should be instilled prior to the procedure.21

GI Decontamination

Multiple methods of gastrointestinal decontamination are available to reduce the bioavailability of an ingested toxin. Most of these methods are outdated and provide little clinical benefit; however, there may be scenarios appropriate for their use.

Emesis induced by syrup of ipecac is not recommended for routine use,22 and we recommend against its use except in the specific scenario of the alert, conscious patient within an hour of a large ingestion of a potentially fatal toxin (not a corrosive substance or hydrocarbon) that is not adsorbed to activated charcoal (AC). Gastrointestinal lavage is the passage of large-bore orogastric tube to administer liquid and aspirate a toxic substance in the stomach. Due to serious risks and limited benefit, there is no place for the routine use of lavage, but use in the critically ill patient with toxic ingestion, depressed mental status, and instability presenting within 1 hour of ingestion may be appropriate.23,24 Use of nasogastric lavage to aspirate liquid poisons does not carry the risk of orogastric lavage and has been demonstrated to reduce poison absorbed.23 Nasogastric aspiration of liquid poison may be performed in patients presenting after ingestion of liquid poison who are still anticipated to have poison remaining in the stomach.

Whole bowel irrigation (WBI) is a method of emptying the gastrointestinal tract in order to limit further absorption of a toxin. This is typically done using a warmed polyethylene glycol–electrolyte solution (PEG–ES) at rates of 0.5–1L/h in the adults, which often requires the placement of a nasogastric or orogastric tube.25 WBI may be performed in select situations, for example, large and potentially fatal ingestions of substances not bound by charcoal such as iron or lead, sustained-release preparations, or in the body packing of illicit substances. It is contraindicated in bowel obstruction, perforation, gastrointestinal hemorrhage, hemodynamic instability, unstable airway, or potential for deterioration of the airway.25

Of all methods of gastrointestinal decontamination, AC has the most potential benefit but is still not recommended for routine use in the poisoned patient.26 AC may be used at 1 g/kg up to 100 g, and is best performed within 1 hour of ingestion with limitations similar to WBI. It decreases the bioavailability of a wide variety of toxins but is not useful for the ingestions of alcohols, corrosives (acids/alkalis), magnesium, potassium, or metals such as iron and lithium. A majority of the adverse effects related to AC are from aspiration or direct administration of charcoal into the lungs.27 Clinicians may sedate and intubate a patient in order to administer WBI or AC, but in doing so must recognize that the risk for aspiration, though small, still exists.

Enhanced Elimination

Enhancing elimination of a toxin is indicated in patients who have decreased elimination of a drug (i.e., renal failure with ingestion of drug that is mainly eliminated in the urine) or in toxins that have a prolonged elimination half-life. Multidose AC may be used in the appropriately alert patient with potential severe toxic or fatal ingestions of carbamazepine, dapsone, phenobarbital, quinine, phenytoin and theophylline, or in cases of ingestion of long-acting or enteric formulations, and in bezoar formation.28 After the initial dose of AC, administer 0.25–0.5 g/kg Q 2–6 hours for up to 12 hours.

Urine alkalinization is method of enhancing elimination of weakly acidic toxins by trapping them in an alkaline urine compartment. This is only recommended as first line for the treatment of moderately severe salicylate poisoning and as second line in the ingestion of fluoride, methotrexate, phenobarbital, 2,4-dichlorophenoxyacetic acid, and mecoprop.29 A urine pH of 8.0 can be achieved by an initial bolus one to two ampules of sodium bicarbonate followed by an infusion of two to three ampules in 1 L of D5W at 1.5 times maintenance with concurrent aggressive repletion of potassium.

Hemodialysis and charcoal hemoperfusion are the most invasive and expensive methods of enhancing elimination of toxins and have the added advantage of improving acid–base and electrolyte imbalances. Salicylate, methanol, ethylene glycol, theophylline, caffeine, carbamazepine, lithium, and procainamide (refer to Table 40-3) are amenable to dialysis.

Antidotes

Although most management of the poisoned patient is supportive care, the judicious use of an antidote is sometimes the only therapy capable to prevent morbidity or mortality. Examples of this are the administration or hydroxocobalamin or sodium thiosulfate for cyanide poisoning, oxygen for carbon monoxide toxicity, digoxin Fab, fomepizole and/or ethanol for toxic alcohol poisoning, or N-acetylcysteine for acetaminophen toxicity, and calcium for calcium channel blocker overdose.

Critically ill patients who present with symptoms justifying reasonable suspicion for poison exposure can also be treated empirically. Examples of such include empirical use of naloxone in patients with respiratory depression and pinpoint pupils or use of pyridoxine for the child in status epilepticus whose household member is being treated for tuberculosis with isoniazid.

Antivenom exists for the hematologic, neurologic, and cytotoxic effects of the two main categories of snakes in the United States (Elapidae and Crotalinae). There are other antivenoms for scorpions and spiders that are available in specific geographic areas of the United States where they are relevant. There are also antivenins for rare, nonindigenous exotic snakes that are imported and used in zoos and research facilities and occasionally used to treat envenomation from exotic animals illicitly imported and kept as pets. These exotic antivenins tend to be available at facilities that must be prepared for such envenomations, such as zoos or the hospitals that serve them.